Field of the Invention
The invention pertains to the area of miniature biochemical and chemical detectors for pathogens, biomarkers, toxins, and other materials, and more specifically to microprocessor-controlled microfluidic platform technologies comprising such miniature biochemical and chemical detectors. In various embodiments the invention provides a framework for and family of platform technologies for a next generation of pathogen, toxin, biomarker, and chemical sensor and analysis systems. The technology can be implemented in a small sized format and notably can be used for food and water safety testing in the field, distribution chain, laboratory, clinic, and home.
General Background
Humans, animals, crops, and the general environment are subject to many threats from pathogens, toxins, and disease. In the testing for these a vast diversity of diverse test frameworks, technologies, laboratory methods, and protocols have been devised, each incrementally building on existing and competing generations of test frameworks, technologies, laboratory methods, and protocols. Although competition among these can in principle reduce costs, in practice the diversity can increase costs and continually set the expenditure bar higher as one or another approach can do a superior job in some aspects but not other aspects. Large laboratories filled with large quantities of various expensive “required” technologies and materials become the entrenched solution. The volumes of manufacturing for the large diversity of evolving laboratory machines and materials are small, preventing meaningful economies of scale from being achieved or even envisioned, these high costs forces geographical and institutional centralization of testing with tremendous throughput, logistic, and economic barriers to the needed levels and most logical settings for monitoring, testing, and diagnosis.
In the approach put forth in the present invention, the immense diversity of aforedescribed evolving technologies and emerging alternative technologies can be mined for ranges of appropriate and adaptable component technologies that can, through careful systems design, be unified into a low cost platform capable of readily addressing many practical problems inherent in the needs for pathogen, toxin, and disease testing and monitoring and readily applicable to large manufacturing and distribution economies of scale. Further, the resulting technology base offers many additional applications to industry, R&D, the world's impoverished, and the economy.
Discussion begins first with a review of pathogens and toxins in food and water, followed by health and disease. This general background provides the setting for appreciating and understanding the value of the present invention.
Safety Improvement Opportunities in Food and Water Systems
There is vast need and concern for food and water safety domestically and worldwide. Outbreaks new of food-borne diseases in packaged, processed, and even locally produced food are ever-present in the developed world (costing lives, health, vast waste, and hundreds of millions of dollars) and of course viciously plague the undeveloped world (costing vast numbers of lives, health, and impeded economic development). Similarly, water quality has also been threatened by contamination, and as populations increase in areas involving farming, industry, mining, natural-gas/shale-oil “fracking,” etc., the concerns are becoming more acute. Water quality is also involved in food safety as contaminated wash or process water can and has cause both biological and chemical food safety incidents. Further, both food and water are perpetual targets for terrorism, contamination by industrial dumping, mining, fossil-fuel drilling, waste-landfill leakage, waste-water handling failures, etc.
FIG. 1a depicts a simplified representation of large-scale commercial food distribution chains. At each point in the chain there is both the opportunity for food safety compromises and food safety testing. Because of the vast degree of (immensely multi-sourced) food aggregation and blending involved in processed foods (including ground meats, washed/packaged salad greens, basketed small tomatoes/fruits, as well as prepared meals, dairy products, and canned items), a small contamination incident or point source can widely propagate through massive amounts of products and geographic area. The ability to inexpensively and rapidly screen for a wide range of food pathogens and pollutants at every point in the chain would provide a tremendous step forward.
FIG. 1b depicts the smaller scale distribution arrangements associated with both “local food” trends in developed nations as well as the long-established systems and arrangements in rural areas and developing countries. Although the scales of individual food volumes are smaller in each instance of the depicted entities and steps than those associated with FIG. 1a, there far is less ability and framework to practically impose regulations, monitoring, and procedures than there are for the entities and steps in FIG. 1a. As a result, again there is considerable exposure to food contamination. Hereto, the ability to inexpensively and rapidly screen for a wide range of food pathogens and pollutants at every point in the chain would provide a tremendous step forward.
FIG. 2a depicts example large-scale water aggregation and distribution arrangements typically found at municipal, county, state, interstate, and in many cases (for example, shared rivers and lakes) international levels. As with the food network depicted in FIG. 1a, a small contamination incident or point source can widely propagate through massive amounts of products and geographic area, and the ability to inexpensively and rapidly screen for a wide range of water pathogens and pollutants at every point in the chain would provide a tremendous step forward.
Similarly, FIG. 2b depicts the smaller scale distribution arrangements associated with village, rural areas, individual farms, and homes found worldwide at all levels of economic development. There far is less ability and framework to practically impose regulations, monitoring, and procedures than there are for the entities and steps in FIG. 2a, and as a result, again there is considerable exposure to contamination. Once again, the ability to inexpensively and rapidly screen for a wide range of food pathogens and pollutants at every point in the chain would provide a tremendous step forward.
Creating a technology that can service such a vast range and scale of safety improvement opportunities in food and water systems must be small, inexpensive, fast, accurate, provide wide ranges of tests, include internal interpretation/analysis, and be easy to use, reliable, and constantly updated. Anything manufactured, be it a testing instrument or consumable items used by it, will be manufactured and distributed at a massive scale. The large manufacturing scale provides significantly many wide-ranging opportunities to reduce costs, create opportunities for a standard framework, and justify ongoing focused R&D to improve performance, capabilities, and ranges of applications. However, such a large manufacturing scale also increases the need for the technology to be realistically envisioned, thought-through, and carefully designed.
FIG. 3a depicts an example representation of how pathogens borne by food and/or water can be ingested by, absorbed by, and/or exposed to an organism (such as a human, animal, plant, etc.). In such a situation, a sample of the food or water can be presented to a pathogen detection process that is used to directly identify pathogens present in the food and/or water sample.
FIG. 3b depicts an example representation wherein pathogens borne by food and/or have already can be ingested by, absorbed by, and/or exposed to an organism and are now present in the organism. If a sample containing the pathogen can be obtained from the organism, that sample can be presented to a pathogen detection process that is used to directly identify pathogens present in that sample. In some cases the pathogen can be present in easily obtained bodily fluids or tissues of the organism, while in other cases biomarkers can be highly localized within tissues or confined fluids of the organism. (Biomarkers will be considered in extensive detail, but for the moment they can be regarded as indicators of a biological state.)
The above discussion motivates the need for testing of pathogens and toxins, at least in food and water. In many cases, however, the approach of FIG. 3b is not possible or not realistic. For example, the pathogen can have already been wiped out by the immune system, or can be in a part of the organism from which obtaining a sample is difficult, or the pathogen can be too rarefied within the organism to be adequately captured in the sample. In such cases, however, the pathogen could have induced a change in the biological state of the organism which can be identified by testing for biomarkers.